Introduction: Although there have been significant contributions from the pharmaceutical industry to clinical practice, several diseases remain unconquered, with the discovery of new drugs remaining a paramount objective. The actual process of drug discovery involves many steps including pre-clinical and clinical testing, which are highly time- and resource-consuming, driving researchers to look for technological interventions that can improve the process efficiency. The shift of modelling technology from two-dimensions (2D) to three-dimensions (3D) for in vitro drug screening is one of such advancements. Three-dimensional models allow for close mimicry of cellular interactions and tissue microenvironments thereby improving the accuracy of results. The advent of this bioprinting technology for fabrication of tissue constructs has shown potential to improve 3D culture models. Areas covered: The present review provides a comprehensive update on a wide range of bioprinted tissue models and appraise them for their potential use in drug discovery research. Expert opinion: Efficiency, reproducibility, and standardization are some impediments of the bioprinted 3D models. In addition, vascularization of the constructs has to be addressed for the bioprinting domain, in the near future. While much progress has already been made with several seminal works, the next milestone will be the commercialization of these models after due regulatory approval.

Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

Aim: We intended to survey the prognostic utility of pretreatment neutrophil-to-lymphocyte ratio (NLR) as a novel prognostic index in recurrent glioblastoma multiforme (R-GBMs) treated with bevacizumab plus irinotecan (BEVIRI). Patients & methods: The present retrospective investigation incorporated the R-GBMs patients who underwent BEVIRI. The pre-BEVIRI NLR was calculated for each patient by utilizing the complete blood count tests obtained on the first day of BEVIRI. Results: The data of a total of 103 patients were analyzed. The ideal cut-off was identified at 3.04 (area under the curve: 60%; sensitivity: 60.3%; specificity 60%) for the pre-BEVIRI NLR. Low-NLR group had significantly longer overall survival times than the high-NLR group (15.8 vs 9.3 months; p = 0.015). Conclusion: NLR might be utilized as a novel biomarker in the prognostic stratification of the R-GBMs treated with BEVIRI.

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Introduction: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the rst-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received rst-line Alectinib as ALK-TKI.Materials and Methods: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a rst-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥40% and low-positive group <40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells.Results: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n=78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n=113) but it was 10.8 months in the low-positive group (n=98) (HR: 0.39; 95% CI, 0.25-0.60, p<0.001). The median OS in the high positive group was not reached, whereas it was 22.8 months in the low positive group (HR: 0.37; 95% CI, 0.22-0.63, p<0.001). ORR was signi cantly higher in the high-positive group (87.2 vs. 68.5%; p=0.002). According to the cutoff values of <20%, 20-39%, 40-59%, and ≥60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥60% group.Conclusion: Our study demonstrated that the e cacy of alectinib varies signi cantly across patient subgroups with different percentages of ALK-positive cells. If these ndings are prospectively validated, the percentage of ALK-positive cells may be used as a strati cation factor in randomized trials comparing different ALK-TKIs.